Labeling and mitotic index data and estimates for the length of the S and M phases of the cell cycle from the literature have been compared with new data obtained over a 24-hr period from various epidermal sites in mouse. It has been found that values obtained at a single time of the day may give misleading results. All data have been interpreted in terms of cell production rates per epidermal proliferative unit (EPU). The final conclusions after consideration of cell production rates, labeling and mitotic indices, epidermal transit times, and epidermal structure are that dorsal and ear skin have rather similar cell production rates while tail and foot rates are 4 to 7 times higher. A comparison has also been made between the mouse results and the available human data. Hairless mouse dorsum appears from structural and proliferative aspects to be the best model for some regions of human skin. A new model has been proposed for epidermal proliferation based on the EPU. The model suggests a role for the Langerhans cells and suggests that there is a program of sequential cellular maturity in the EPU originating at the level of a central basal stem cell through committed proliferative cells and ending with cell loss from the skin surface.